AAN: Caution Urged in Stenting Veins in MS Patients

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Remind patients that these are unproven, invasive treatments that have limited science to support their outcomes.

Note that this study was reported as a topic review and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

TORONTO -- Invasive procedures designed to correct venous blood flow in multiple sclerosis patients should not be performed until clinical trials can prove that the treatment is safe and effective, physicians here suggested.

John Corboy, MD, professor of neurology at the University of Colorado School of Medicine, Denver, reviewed studies performed by Paolo Zamboni, MD, professor of vascular surgery at the University of Ferrara in Italy. Zamboni has been the leading investigator into the possibility that chronic venous insufficiency could be a causative problem in multiple sclerosis.

"The logic for this is based on the fact that multiple sclerosis plaques are perivenular and that multiple sclerosis and chronic venous insufficiency share several features," Corboy said at the annual meeting of the American Academy of Neurology. Among those features are the expression of adhesion molecules, hyperactivation of matrix metalloproteinases, macrophage and T-cell infiltration, and iron deposition in the location of the lesion.

In an expanded study published in 2009 (J Neurol Neurosurg Psych 2009; 80(4): 392-99), the researchers looked at extracranial flow in the jugular and vertebral veins among 65 multiple sclerosis patients and 235 controls. They noted abnormalities in the blood flow in the multiple sclerosis patients and performed balloon angioplasties in those 65 patients, Corboy said.

That study found what the researchers termed a "dramatic" association between multiple sclerosis and venous abnormalities, with an odds ratio of 43 (95% CI 29 to 65, P=0.0001).

"After the procedure there was a small drop -- and I would emphasize small drop -- in the pressure gradient of about 2 to 3 cm of water," Corboy said. "They did report statistically significant reductions in relapse rate, an increase in the number of patients who were free from relapse after 18 months, a reduction in magnetic resonance imaging gadolinium enhancing lesions, and improvements in quality of life. In this uncontrolled fashion it was perceived that these were improvements for the patients." In an uncontrolled study these are likely to reflect regression to the mean -- a phenomenon frequently observed in the placebo arms of MS clinical trials.

He also noted that a study from the University at Buffalo, according to the institution's press release, described similar numbers when comparing 280 multiple sclerosis patients and 161 controls.

However, Corboy suggested several limitations of the studies, including difficulty in replication of the work and the unblinded nature of the trial. "When I showed this information to our pathologists they said, 'Wow. A couple of centimeters of water . . . that's nothing. Who would ever notice that?' There is no pathological or MRI correlation. We need controlled trials to see true effects of stenting."

Corboy said doctors who began treating chronic venous insufficiency at Stanford University, in Stanford, Calif., have halted their work following two devastating adverse events. In one case, a patient was stented, put on warfarin to prevent stent-related thrombosis, and then developed a fatal intracranial hemorrhage. In a second case, the stent mobilized and became lodged in the right atrium of the heart, requiring cardiac procedures to remove it.

Corboy acknowledged that the reports from Italian investigators have already gotten interest from multiple sclerosis patients but said that while early studies indicate there may be improvement in blood flow, the risks of the procedure may be too great to proceed without completing major, controlled clinical trials.

"Many of you are quite aware of this work and have been getting many phone calls from angiographers and other people about this procedure," Corboy said in his lecture updating developments in multiple sclerosis -- part of an all-day clinical review of neurologic developments. "I would not recommend it until we had a much better idea whether this approach has any merit whatsoever."

Lily Jung, MD, medical director of the Neurology Clinic and chief of neurology at Swedish Medical Center, Seattle, concurred with Corboy: "It is absolutely too early to recommend this procedure. There are a lot of methodological issues with the studies, and until those have been standardized in a randomized, double-blinded study and found to be effective, it is unreasonable to suggest that this procedure is ready for prime time."

She told MedPage Today, "There are reputable centers that are now beginning to look at the first step, which [is] identifying whether, in fact, multiple sclerosis patients have the finding suggested by Dr. Zamboni to be present. It is then another big leap to decide whether the procedure can be safely performed in humans. [And that is] before even going to full-blown clinical trials."

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